Histone Deacetylase Activity In Chronic Lymphocytic Leukemia.

Abstract 4622

Elevated histone deacetylase (HDAC) enzyme levels have been described in patients with carcinoma and leukemia. Using HDAC inhibitor (HDACi) to treat carcinoma has been promising and is currently undergoing intense research. In order to be better in using HDACi to treat chronic lymphocytic leukemia (CLL), HDAC isoenzyme levels were measured in 32 patients with CLL and compared with 17 normal volunteer controls. Peripheral blood CD20⁺ cells from patients with CLL and normal volunteer controls were isolated by using Progenitor Cell Isolation Kits (Miltenyi Biotec, Auburn, CA). Isolated CD20⁺ cells were confirmed by flow cytometry studies to have more than 92% purity. Patient and control CD20⁺ cells were then lysed in denaturation buffer. Total RNA was extracted, then cDNAs were prepared and quantitative RT-PCR was performed using premixed primer and FAM- and TAMRA-labeled probes obtained from ABI. The results showed: 1) HDAC1, -3, -6, -7, -9, and -10 and SIRT1, -2, and -6 were significantly over-expressed, suggesting that, in CLL, elevated HDAC activity are not restricted to one class. Therefore, HDAC inhibitor therapy may need to be directed to more than one specific class of HDAC; 2) Patients with ZAP70⁺ were associated with more advanced Rai clinical stage and higher HDAC activity than Zap70^– patients and HDAC activity were correlated to the expression levels of CD44 and Pin1, suggesting that higher HDAC values may indicate a poor prognosis and more advanced disease stage.